Electrical field stimulation of the full-thickness rabbit ileum increases the luminal electrical negativity, increases the short circuit current, reduces the tissue conductance, and causes chloride secretion. These responses are prevented by tetrodotoxin. In addition, tetrodotoxin greatly enhances the mucosal to serosal movement of Na and Cl and increases tissue conductance. The intent of the proposed studies is to determine the identity of the chemical transmitter that mediates the responses to electrical field stimulation, to determine the site and mechanism of action of the transmitter, and to assess the site and mechanism through which tetrodotoxin increases the absorption of Na and Cl by the epithelium. I will try to identify the transmitter by determining whether the response to stimulation can be prevented by autonomic antagonists, antagonists of endogenous substances capable of causing Cl secretion, somatostatin and lactamimide. I will also try to determine what substances are released by electrical stimulation by collaborating with other investigators who have developed assays for peptide hormones known to be present in the intestine, e.g., Drs. Gaginella and O'Dorisio of Ohio State University (VIP). Because the responses to electrical stimulation may vary with the segment of the alimentary tract. we will study jejunum and colon of the rabbit, and in other species. We will also determine if these responses are present in the intestine of man.